The Aids Mirage by Professor Hiram Caton (23/3/1995)

Junk science goes belly-up
"I knew that if this retrovirus was the cause of AIDS . . . we would need to convince the academic community as totally, as widely, and as quickly as possible."—Robert Gallo.

"Scientists in the United States are forced to produce results, which sometimes warps their sense of ethics."—Luc Montagnier.

"The incredible Gallo incident will be a scar on the history of science."—Don Francis

"Gallo was certainly committing open and blatant scientific fraud."—Joseph Sonnabend.

Australian AIDS science is a mosaic of research whose key elements stem from Robert C. Gallo, MD, Director of the Laboratory for Tumor Cell Biology, National Cancer Institute. He made world headlines in April 1984 as the discoverer of the "AIDS virus". The media rejoiced that the path to vaccine prevention of AIDS was open, and that a vaccine was likely be ready for trial in two to three years. His contribution did not end there. Dr Gallo devised a test for the presence of the virus and mastered the art of growing the virus in the large quantities needed for research. The media applauded that lives would be saved by protecting blood banks and that accurate epidemiological work could now be undertaken.

The worldwide conviction that HIV is the cause of AIDS dates from this moment. The event was packaged to produce optimal belief. Health Secretary Margaret Heckler greeted the press conference in the National Academy of Sciences auditorium packed with journalists and television crews. She declared that "today we add another miracle to the long honor roll of American medicine and science. Today's discovery represents the triumph of science over a dreaded disease." The discovery was a sorely needed answer to the chorus of critics who complained that the Reagan administration was doing too little to combat AIDS. Heckler dazzled critics with Gallo's American "miracle " and reminded the public of the gratitude it owed to medicine for triumphing over "dreaded disease". Then it was Dr Gallo's turn. He outlined the science of his virus, HTLV-III, emphasising that it had been shown to cause immunosuppression. He discussed his work's relationship to other research, particularly the work of the Pasteur Institute, and conceded that HTLV-III "may be" the same as the Institute's LAV virus.

The journalists reporting this event didn't notice the telltale signs that there was something fishy about the occasion. An obvious anomaly was that the announcement was made prior to publication of the articles presenting the evidence. A firm rule of scientific publication bans this practice. It hobbles the critical reception because scientists cannot comment on research that they haven't seen. Further, prepublication celebrity suborns scientists to see in the articles what the media have acclaimed. In this case the priming was unusually strong. By designating Gallo's findings the shining path to victory over AIDS, Secretary Heckler in effect laid down the orthodoxy governing AIDS research funding. But this in turn set limits to critical opinion. As it happened, there were quite a few scientists who gave Gallo's claims little credence. But their voices were not heard because journalists didn't search for critical comment; and in a very short time the orthodoxy was so entrenched that critical views seemed aberrant, even "loony".

The other visible anomaly was the Pasteur virus. On the day prior to the press conference, The New York Times published a front-page story sourced to Dr James Mason, the CDC chief. He gave full credit to the Pasteur team for isolating the new retrovirus a year previously, for proving that it caused AIDS, and for developing immunoassay tests. On the surface, this was only a priority dispute that left a Cabinet member furious that a subordinate had rained on her picnic. But had reporters looked beneath the surface, they would have found significant misconduct stemming from rivalry but also doubts that either virus was pathogenic. Here are a few things that journalists missed at that crucial moment in the creation of AIDS science.

Relations between Gallo and the Pasteur Institute became hostile when the US Patent Office shut the door on the Institute's application for an immunoassay patent. The Institute made its initial application for a US patent in 1983, but it stalled. Gallo and the US Department of Health applied for a patent on the day of Heckler's announcement. It was granted almost at once. The French cried "Foul!" The public wrangling threatened to undermine the integrity of AIDS science. It was settled by an unprecedented agreement between heads of state (Reagan and Jacques Chirac), which gave a percentage of US royalties on test kits to the French. Although Gallo and Montagnier professed satisfaction with this outcome, the "kiss and make up" arrangement was part of the deal. In reality the French believed that they had scored only a small victory over "Robert Gallo's steamroller". The French actually believed that Gallo had no rightful propriety in the kits because his virus and his cell lines derived from their virus. In June 1994, the Director of the Pasteur Institute renewed the old objections. Dr Maxime Schwartz wrote to NIH Director Dr Harold Varmus that the agreement must be renegotiated because the previous agreement was based on "a cover-up of the true facts" and "deliberate fabrication" that gave a specious basis for American claims. "The French test kit was developed in the absence of any input from the American scientists," Schwartz told Varmus, "whereas there is no evidence that the American test could have been developed if the American scientists had not received the French virus."

The Americans agreed to renegotiate, and after strenuous bargaining, the French demands were met. The reason probably was that Schwartz's letter coincided with a detailed report, in June 1994, by the Inspector-General of the US Department of Health and Human Services on the issues between Gallo and the Pasteur Institute. The report finds entirely in favour of the French. It states that Gallo obtained his patent by unlawfully concealing relevant information from the patent office attorney; that he admitted this unlawful act; that Pasteur scientists were first to discover the AIDS virus, to isolate it successfully from several AIDS patients, to describe it in a scientific article, and to use it to make a diagnostic blood test for antibodies to the AIDS virus. In short, miraculous American science has no entitlement at all to patent, or to patent royalties, or to credit for discovering the AIDS virus. Professor Frederick Richards, who headed a previous investigation of Gallo's misconduct, called for misconduct hearings to be reopened. He referred to a 1987 study of similarities between the Gallo and the Pasteur viruses that was concealed from his committee. The study, by the Los Alamos National Laboratory, asserted that Gallo's claim to independent discovery was a "double fraud". "The major purpose of this whole investigation", Richards stated "was to find out whether [Gallo's lab] stole the [Pasteur] virus. The answer is, they stole the virus. But [my committee] didn't know that at the time."

These are the latest of a long series of findings of misconduct in the Gallo laboratory. A previous investigation the Office of Research Integrity found that Gallo lied when he denied growing the French cell culture in his lab; that he "misrepresented and misled in favour of his own research findings or hypotheses"; that his lab management was "irresponsible", especially in his inability to document crucial steps of his experiments; that the photo of HTLV-III published with his path-breaking viral discovery was identical to the photo published by the Pasteur team a year earlier; that he reported in a Lancet article no adverse reactions to a trial vaccine when in fact both (African) subjects of the trial had died; that one of his staff and co-authors was convicted of a felony in connection with research, while his deputy laboratory chief was indicted.

Nor is that the end of it. In June 1994 researchers challenged a Gallo study purporting to demonstrate the therapeutic value of a compound to treat KS. The study seemed methodogically suspect to the University of Arizona team. The statistical data seemed irregular and the photos published with the article did not seem right. So they undertook to replicate the findings. They even replicated an experimental error that they suspected might account for the dubious results. The attempt was unsuccessful. Their original suspicions were confirmed and they reported "serious systematic errors and omissions". The implication of their critical article was that Gallo's evidence of therapeutic benefit was at best unsound and at worst faked. The Arizona team submitted their findings to Science, the publisher of Gallo's paper. The journal's reviewers rejected the submission on the grounds it was "without serious merit and their experiments are an extraordinary waste of time and effort". They accordingly submitted to the Journal of the American Medical Association, which printed it together with an explanation of the article's rejection. The authors stated that the most troubling aspect of the contretemps

"has been the reticence and obstacles encountered to public airing of our questions and the inability of the peer review process to correct itself once errors and inconsistencies were pointed out and bolstered by further experimentation".
Another aspect of the case was conflict of interest among the co-authors of the Gallo article. One was a scientist on the staff of the pharmaceutical firm that manufactures the compound whose benefits were validated.

What does this expose of chicanery mean for the evaluation of the hypothesis that HIV is the cause of AIDS?

In the first instance it shows once again that peer review, the supposed watchdog of science's quality and integrity, is heavily compromised by patronage loyalties. It is awesome that Gallo's plagiarism of the Pasteur micrograph of HIV could be published in the same journal without the plagiarism being detected by either the submission's reviewers or the journal editor. Some, of course, noticed the plagiarism straight away. In the ideal world that science is said to occupy, a letter pointing out this serious misconduct would have been sufficient for a retraction and the offender's dismissal. In the event, a costly and protracted high-level investigation was needed to establish this banal fact. Even then Gallo successfully defended himself by a diversionary tactic. The institutional rule that chiefs bear responsibility for the work of their subordinates was derailed by the simple device of blaming the lab photographer for a "stupid mistake". Gallo was not dismissed nor was his prestige visibly impaired.

This is a cameo of the science culture in which sleaze thrives. At every stage of the rise and progress of the HIV hypothesis toward dogma, its influence is apparent. The belief that HIV is the necessary and sufficient condition for AIDS depends on the credibility of Gallo's initial claims to this effect. The Pasteur team made this claim only tentatively. It was converted to a certainty by a promotional campaign conducted in the scientific press. The first shot was fired by the New Scientist, which published a story touting Gallo's findings in early April 1984. The story was based on science writer Martin Redfearn's interview with Gallo, who had provided him with prepublication copies of the Science articles. The New Scientist resisted all entreaties by Gallo's British colleagues that publication prior to the appearance of the Science articles was unethical. The CDC then moved quickly to spoil Gallo's triumph. It had allied itself with the Pasteur Institute in a power struggle with the National Cancer Institute. It planted The New York Times story through The Times' science writer, Dr Lawrence Altman, who had been a CDC scientist. The Gallo side struck back through its London ally, Nature, which published its review of Gallo's discovery only four days after the press conference. The article's title left no doubt: "Causation of AIDS Revealed". The subtitle stated that "the retrovirus responsible for AIDS has been identified by Gallo's group at NIH; Montagnier's group in Paris has helped". By assigning the Pasteur Institute a position to the rear of Gallo in the Nobel prize queue, the author reversed the implication of The New York Times article that Gallo did nothing more than to discover the Pasteur virus a second time. The Nature article claims that Gallo's publications provide "compelling evidence for a primary association of this virus with the disease". The author was Jerome Groopman, MD, one of Gallo's Harvard friends.

Thus, within a period of one month, four highly credible publications endorsed the idea that the cause of AIDS had been "revealed". To reveal the discovery, these publications had to conceal the fact that AIDS science had not advanced since Montagnier's modest claims a year earlier. The modest claims were inflated by the Pasteur side solely to counter Gallo's overreaching. The exercise is a classic case of ambition interacting with media celebrity to create convictions unsupported by evidence. The process is called "truth management" —the orchestration of prestige and authority to create, from the fallible surmises of a small group of friends, the appearance of incorrigible certainty girding the Earth. The basic trick is to capture the free-floating human sense of recognition (the Eureka feeling) and weld it to a specific set of beliefs. This effect automatically converts into certainty any belief to which it is attached.

Generally speaking, truth management is merely one application of the arts of persuasion, promotion, and propaganda. It is not distinguished by the novelty of its devices, but in the boldness of their application to the one patch of modern culture that is supposed to be impervious to these arts. The details of the promotion of the viral theory show that managing truth is not an occasional lapse from rigid integrity. It is an indispensable tool, used daily by editors, grant bodies, policy-makers and the like, to shape the direction of otherwise "chaotic" science. To use an economic analogy, it replaces individualistic laissez-faire in discovery with "research management plans".

Managed truth need not be any more delusional than the laissez-faire alternative. The mystique of authority and the charisma of Eureka are human constants not easily eliminated from social processes. Life would be the poorer without them. Research management schemes instituted in the wake of the Dawkins reform of the tertiary sector were a response to the chaos of many thousands of academics pursuing their individual or small-group convictions. Those schemes are similar to corporate or defence-sector research management, both of which have yielded a harvest of useable discoveries over long periods. But there is skilful and unskilful management. Looking back on AIDS research management, the error was to place all the funding eggs in the one basket of the HIV hypothesis. Circa 1983-4, there were congeries of supportable hypotheses about the cause of AIDS. It was appreciated that the uncertainty of hypotheses stemmed from basic ignorance about the immune system. This predicament suggested that as research advanced, hypotheses would rapidly change, at the very least in the direction of refinement. The prudent strategy, then, would have been to support research along different tracks, to provide insurance against placing all bets on one horse that might not finish. The opposite strategy was the one chosen. The choice was never explicitly evaluated. The evaluation process was pre-empted by a coterie who mystified AIDS research by engineering the conviction that HIV is the cause of AIDS. The downstream costs were predictable. When all funding for research intended to have an urgent public use is placed in one basket, the funding body is left empty-handed if the hypothesis is barren. Public commitment to a barren hypothesis introduces another prestige factor making it difficult to revise the hypothesis. That factor is the loss of face involved in admitting error. The need to keep up the appearance of the reliability of the scientific consensus thus locked AIDS science into a no-win predicament that becomes ever more intransigent as the futility of the hypothesis becomes ever more apparent.